TDF Use in HBV-HIV Coinfection Linked With Kidney, Bone Issues
Patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) who take tenofovir disoproxil fumarate (TDF) may have worsening renal function and bone turnover, according to a small, prospective cohort study in HIV Medicine.
“In this HBV-HIV cohort of adults with high prevalence of tenofovir use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinicians’ awareness,” lead author Richard K. Sterling, MD, MSc, assistant chair of research in the Department of Internal Medicine of Virginia Commonwealth University, Richmond, told Medscape Medical News in an email.
TDF is a common component of antiretroviral therapy (ART) in adults coinfected with HBV and HIV. The drug is known to adversely affect kidney function and bone turnover, but few studies have evaluated these issues, the authors write.
Sterling and colleagues enrolled adults coinfected with HBV and HIV, who were taking any type of ART, in their study at eight sites in North America.
The authors assessed demographics, medical history, current health status reports, physical exams, and blood and urine tests. They extracted clinical, laboratory, and radiologic data from medical records, and they processed whole blood, stored serum at -70 °C (-94 °F) at each site, and tested specimens in central laboratories.
The researchers assessed the participants at baseline and every 24 weeks for up to 192 weeks (3.7 years). They tested bone markers from stored serum at baseline, week 96, and week 192. And they recorded changes in renal function markers and bone turnover over time.
At baseline, the median age of the 115 patients was 49 years; 91% were male, and 52% were non-Hispanic Black. Their median body mass index (BMI) was 26 kg/m2, with 6.3% of participants underweight and 59% overweight or obese. The participants had been living with HIV for a median of about 20 years.
Overall, 84% of participants reported tenofovir use, 3% reported no HBV therapy, and 80% had HBV/HIV suppression. In addition, 13% had stage 2 liver fibrosis and 23% had stage 3 to 4 liver fibrosis. No participants reported using immunosuppressants, 4% reported using an anticoagulant. 3% reported taking calcium plus vitamin D, and 33% reported taking multivitamins.
Throughout the follow-up period, TDF use ranged from 80% to 92%. Estimated glomerular filtration rate (eGFR) dropped from 87.1 to 79.9 ml/min/1.73m2 over 192 weeks (P < .001); but eGFR prevalence <60 ml/min/1.73m2 did not appear to change over time (always <16%; P = .43).
From baseline to week 192, procollagen type 1 N-terminal propeptide (P1NP) dropped from 146.7 to 130.5 ng/ml (P = .001), osteocalcin dropped from 14.4 to 10.2 ng/ml (P < .001), and C-terminal telopeptides of type I collagen (CTX-1) dropped from 373 to 273 pg/ml (P < .001).
Predictors of decrease in eGFR included younger age, male sex, and overweight or obesity. Predictors of worsening bone turnover included Black race, healthy weight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level.
Monitor Patients With HBV and HIV Closely
“The long-term effects of TDF on renal and bone health are important to monitor,” Sterling advised. “For renal health, physicians should monitor GFR as well as creatinine. For bone health, monitoring serum calcium, vitamin D, parathyroid hormone, and phosphate may not catch increased bone turnover.
“We knew that TDF can cause renal dysfunction; however, we were surprised that we did not observe significant rise in serum creatinine but did observe decline in glomerular filtration rate and several markers of increased bone turnover.”
Sterling acknowledged that limitations of the study include its small cohort, short follow-up, and lack of control participants who were taking TDF while mono-infected with either HBV or HIV. He added that strengths include close follow-up, use of bone turnover markers, and control for severity of liver disease.
Joseph Alvarnas, MD, a hematologist and oncologist in the Department of Hematology & Hematopoietic Cell Transplant at City of Hope Comprehensive Cancer Center in Duarte, California, told Medscape Medical News that he welcomes the rigor of the study.
“This study provides an important reminder of the complexities of taking a comprehensive management approach to the care of patients with long-term HIV infection,” Alvanas wrote in an email. He was not involved in the study.
“More than 6 million people worldwide live with coinfection,” he added. “Patients coinfected with HBV and HIV have additional care needs over those living with only chronic HIV infection. With more HIV-infected patients becoming long-term survivors who are managed through the use of effective ART, fully understanding the differentiated long-term care needs of this population is important.”
Debika Bhattacharya, MD, a specialist in HIV and viral hepatitis coinfection in the Division of Infectious Diseases at UCLA Health in Los Angeles, joined Sterling and Alvarnas in advising clinicians to regularly evaluate the kidney and bone health of their coinfected patients.
“While this study focuses the very common antiretroviral agent TDF, it will be important to see the impact of a similar drug, tenofovir alafenamide (TAF) — which has been associated with less impact on bone and kidney health — on clinical outcomes in HBV-HIV coinfection,” Bhattacharya, who also was not involved in the study, wrote in an email.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funded the study. Sterling has served on boards for Pfizer and AskBio, and he reports research grants from Gilead, Abbott, AbbVie, and Roche to his institution. Most other authors report financial relationships with pharmaceutical companies. Alvarnas reports no relevant financial relationships. Bhattacharya has received a research grant from Gilead Sciences, paid to her institution.
HIV Med. Published online May 15, 2022. Full text
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